Olfactory neurons have the unique ability to reinnervate the adult CNS in mammals. The turnover and replacement of olfactory neurons throughout life suggests that mechanisms of development, turnover and post-lesion reinnervation are fundamentally similar. However, while neurogenesis and axon outgrowth may be similar in these three processes, the target environment presented by the olfactory bulb in development, turnover and regeneration are profoundly different. Preliminary results from this laboratory, taken with other new findings, suggest that glial cells play a critical role in the development of neural connections and the formation of local circuits. By contrast, adult glial cells react to injury/deafferentation to contribute to an environment hostile to reinnervation. Since olfactory axons do successfully reinnervate the bulb, bulb astrocytes, olfactory neurons or both may have unique properties. LM- EM immunohistochemical and deafferentation and neural transplantation studies are proposed to contrast neuron-glial interactions in development and reinnervation, to test the ability of bulb astrocytes to support reinnervation by ectopic neurons and to test the ability of olfactory neurons to grow through or modify glial scars in the spinal cord. We have shown that the olfactory nerve is necessary to the developmental expression of transmitter phenotype in a population of bulb neurons (DA cells). These and substance P neurons have a "trophic" dependency on the olfactory nerve in the adult. New results indicate that this transneuronal or trophic dependence extends to other bulb neurons. Experiments are proposed to define the cellular basis for this phenomenon and to establish which bulb transmitters are and are not nerve dependent. Tissue culture experiments will determine whether molecules specific to olfactory neurons have selective or general trophic effects on transmitter specific populations of bulb neurons. The goal of this research is to test novel hypotheses of the unique developmental, regenerative and trophic capacities of olfactory neurons. Understanding of these unique capacities may provide new approaches for treating developmental and degenerative disorders in the CNS.